Exposure to psychosocial stress produces rises in body temperature of as much as 2oC in rats. The applicant has generated data that support the hypothesis that stress "hyperthermia" is actually a fever (i.e. an elevation in thermoregulatory set point), caused by endogenous pyrogens and prostanoids. Cytokines are released during stress-induced fevers and the applicant has found that exposing a rat to a novel environment results in an increase in concentrations of IL-6, a mediator of inflammation and immunity. Pretreatment with antiserum to TNF-alpha results in an increase of stress fevers. Evidence is also presented that adrenalectomized rats develop larger stress-induced fevers and increased plasma concentrations of IL-6 which is reversed when replacement corticosterone is given. Infusion of RU38486 into the anterior hypothalamus suggests that glucocorticoid negative feedback on stress induced fever and IL-6 rises occur at the level of the central nervous system. Furthermore, injection of beta-adrenoceptor blockers into the CNS attenuates both stress-induced fevers and the rise of IL-6 cytokines. The aims of this study are to: 1) determine the role and site of action of beta-adrenoceptors in modulating stress-induced rises in body temperature and circulating cytokines; and 2) determine the role and site of action of circulating glucocorticoids in modulating stress-induced rises in body temperature and circulating cytokines.